Until about five years ago, the very idea that peptide hormones might be made anywhere in the brain besides the hypothalamus was astounding. Peptide hormones, scientists thought, were made by endocrine glands and the hypothalamus was thought to be the brains' only endocrine gland. What is more, because peptide hormones cannot cross the blood-brain barrier,researchers believed that they never got to any part of the brain other than the hypothalamus, where they were simply produced and then released into the bloodstream. But these beliefs about peptide hormones were questioned as laboratory after laboratory found that antiserums to peptide hormones, when injected into the brain, bind in places other than the hypothalamus, indicating that either the hormones or substances that cross-react with the antiserums are present. The immunological method ofdetecting peptide hormones by means of antiserums, however, is imprecise. Cross-reactions are possible and this method cannot determine whether the substances detected by the antiserums really are the hormones, or merely close relatives. Furthermore, this method cannot be used to determined the location in the body where the detected substances are actually produced.
New techniques of molecular biology, however, provide a way to answer these questions. It is possible to make specific complementary DNA's (cDNA's) that can serve as molecular probes to seek out the messenger RNA's (mRNA's) of the peptide hormones. If brain cells are making the hormones, the cells will contain these Mrna'S. If the products the brain cells make resemble the hormones but are not identical to them, then the cDNA's should still bind to these mRNA's, but should not bind as tightly as they would to mRNA's for the true hormones. The cells containing these mRNA's can then be isolated and their mRNA's decoded to determine just what their protein products are and how closely the products resemble the true peptide hormones.
The molecular approach to detecting peptide hormones using cDNA probes should also be much faster than the immunological method because it can take years of tedious purifications to isolate peptide hormones and then develop antiserums to them. Roberts, expressing the sentiment of many researchers, states: "I was trained as an endocrinologist. But it became clear to me that the field of endocrinology needed molecular biology input. The process of grinding out protein purifications is just too slow." If, as the initial tests with cDNA probes suggest, peptide hormones really are made in the brain in areas other than the hypothalamus, a theory must be developed that explains their function in the brain. Some have suggested that the hormones are all growth regulators, but Rosen's work on rat brains indicates that this cannot be true. A number of other researchers propose that they might be used for intercellular communication in the brain.